Protocol violations are changes in the conduct of a IRB-approved research protocol that are under the investigator’s control and made without prior IRB approval. Incidents are any problematic or unanticipated events that are not protocol violations and that may adversely impact on the study participants or the conduct of the study. You must report all major study-related protocol violations and incidents to the IRB/HRPP.

Major Incident including, but not limited to problem with consent or recruitment process, significant complaint or concern, lapse in study approval, loss of adequate resources, potential breach of confidentiality of confidentiality.

Potential breaches of privacy or confidentiality: Within 48 hours of awareness

Investigators may have reporting requirements (e.g., to an industry sponsor, the FDA or the NIH) in addition to HRPP reporting requirements. These requirements may be more strict. It is the investigator’s responsibility to know and comply with these additional requirements.

Submitting in iRIS

Follow these steps to submit the report. For additional assistance, read the quick guide called "Submitting Post-approval Forms" in the Help section of iRIS.

Open the first study again and click on the Protocol Violation/Incident Report Form link.

Click the "Apply to Multiple" icon next to the correct form.

Check the boxes next to the studies for which you wish to submit this form. Click the "Save a Copy of the Selected Form" button.

You will then need to open each of the studies you selected, open the copied form and submit the form.

What Are Protocol Violations?

Protocol violations are any unapproved changes, deviations or departures from the study design or procedures of a research project that are under the investigator’s control and that have not been reviewed and approved by the IRB. Protocol violations are divided into two categories: major (reportable) or minor (non-reportable).

Major (reportable) protocol violations are any unapproved changes in the research study design and/or procedures that are within the investigator’s control and not in accordance with the IRB-approved protocol that may affect the participant's rights, safety or well-being, or the completeness, accuracy and reliability of the study data. Report all major violations to the HRPP/IRB using the Protocol Violation/Incident Report Form in iRIS.

Failing to obtain informed consent prior to any study-specific tests/procedures.

Failing to follow protocol procedures that specifically relate to the primary safety or efficacy endpoints of the study.

Minor (non-reportable) protocol violations (also known as protocol deviations) are any unapproved changes in the research study design and/or procedures that are within the investigator’s control and not in accordance with the IRB-approved protocol that do not have a major impact on either the participant’s rights, safety or well-being, or the completeness, accuracy and reliability of the study data.

Do not report minor protocol violations to the IRB/HRPP, but document them in the study files.

Examples of minor protocol violations include, but are not limited to:

Routine safety lab work for a participant without new clinical concerns and a history of previously normal lab values is inadvertently omitted at a study visit or performed outside the protocol-defined window. The lab will be performed at the next opportunity and is expected to remain within normal limits.

Investigators miss giving a study required self-administered quality of life questionnaire to a participant.

What are not considered to be protocol violations? Changes, deviations or departures from the study design or procedures that are due to a study participant’s non-adherence are not considered to be protocol violations. However, you should document study participant non-adherence to the study design and/or procedures in the research records and report this to the IRB/HRPP as an incident if the event(s) adversely impacts the study participant’s safety or well-being, or if a pattern of protocol departures indicate a need for changes in the protocol or informed consent document(s).

What Are Incidents?

Major (reportable) incidents are any problematic or unanticipated events involving the conduct of the study or participant participation that may occur during the course of the research project. Report all major incidents to the HRPP/IRB.

The review of these incidents it time sensitive: Submit a Protocol Violation/Incident Report Form in iRIS within 48 hours of the PI’s awareness of the potential breach.

The IRB collaborates with the UCSF Privacy Office to investigate these incidents to meet state and federal regulatory obligations. Investigations must be completed within a short time frame in order to avoid penalties and/or late reporting fines for the institution.

Some examples of major incidents involving privacy or confidentiality:

If you must implement changes to the protocol in order to eliminate or reduce an apparent immediate hazard to the safety of research participants or others, report such changes to the IRB within 10 working days of initiating the changes in the study procedures. In the report, explain whether a modification to the IRB Application/protocol and/or consent document(s) is necessary.

Reminder: Federal regulations require that you receive prior IRB approval for other changes to your study — even minor or sponsor-approved changes.

Example: You must immediately reduce the study drug dose or discontinue a study treatment based on new toxicity information from an interim Data Safety Monitoring Board review or a study sponsor report. In this case, a change in the approved study drug dose may be implemented immediately, with subsequent submission of a corresponding modification application.

Minor (non-reportable) incidents are any events involving the conduct of the study or participant participation that may occur during the course of the research project but which is not problematic or involve significant potential to harm the participant(s) or others. Do not report minor incidents to the IRB/HRPP.

Report event to OHRP, appropriate University officials and study sponsors and FDA (for studies under FDA regulatory oversight) if a full IRB panel review determines that the event report is an UP or (after investigation) determines an instance of serious or continuing noncompliance.

Flag the report and monitor the study for additional violation or incident reports.

An unexpected, research-related event where the risk exceeds the nature, severity, or frequency described in the protocol, study consent form, Investigator’s Brochure or other study information previously reviewed and approved by the IRB.

Noncompliance is defined as: failure to follow state or federal regulation, or the University policies, or the requirements of the VHA Handbook 1200.5, or determinations of the IRB for the protections of the rights and welfare of study participants.

Serious Noncompliance is defined as: failure to follow state or federal regulations or University policies or determinations of the IRB for the protection of the rights and welfare of study participants and that, in the judgment of the IRB, results in, or indicates a potential for a) a significant risk to enrolled or potential participants or others, or b) compromises the effectiveness of the UCSF HRPP or the University.

Continuing Noncompliance is defined as: a pattern of noncompliance that continues to occur after a report of noncompliance and a corrective action plan have been reviewed and approved by the IRB.

Continuing Noncompliance: Continuing noncompliance is a persistent failure to adhere to the laws, regulations, or policies governing human research.

Serious Noncompliance: Serious noncompliance is a failure to adhere to the laws, regulations, or policies governing human research that may reasonably be regarded as:

(1) Involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff, or others; or

(2) Substantively compromising the effectiveness of a facility’s human research protection or human research oversight programs.

Unanticipated (Unexpected): The terms “unanticipated” and “unexpected” refer to an event or problem in VA research that is new or greater than previously known in terms of nature, severity, or frequency, given the procedures described in protocol-related documents and the characteristics of the study population.